反应详情

To a solution of 5 g of 2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxylic acid in a mixed solvent of 50 ml of dimethylformamide and 50 ml of acetone is added 6.5 ml of triethylamine and the solution is stirred. Under cooling at 15°-18° C. 2.2 g of ethyl chlorocarbonate is added dropwise for 10 minutes and the whole is stirred at room temperature for 40 minutes. Then, 3.3 of 1-propyl-2-aminomethylpyrrolidine is added and the reactant is stirred at room temperature for 40 minutes. After it is allowed to stand for 19 hours, excess triethylamine and acetone are distilled off and the resulting residue is slowly poured into 400 ml of water with stirring. Under ice-cooling, crystals are precipitated thoroughly and collected by suction filtration. The crystals are washed with water and dried. The filtrate, aqueous layer is further extracted with chloroform three times, and the extract chloroform layer is washed with aqueous sodium bicarbonate solution and water and dried. The chloroform is distilled off under reduced pressure and to the residue obtained is added isopropanol. Crystals are deposited and collected by suction filtration. Both the crude crystals are put together and recrystallized from isopropanol/methanol (1/1) to give crystals of N-(1-propyl-2-pyrrolidinylmethyl)-2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxamide, m.p. 177°-180° C.

1. temperatureUnder cooling at 15°-18° C
2. stirringthe whole is stirred at room temperature for 40 minutes
3. stirringthe reactant is stirred at room temperature for 40 minutes
4. distillationexcess triethylamine and acetone are distilled off
5. additionthe resulting residue is slowly poured into 400 ml of water
6. stirringwith stirring
7. temperatureUnder ice-cooling
8. customcrystals are precipitated thoroughly
9. filtrationcollected by suction filtration
10. washThe crystals are washed with water
11. customdried
12. extractionThe filtrate, aqueous layer is further extracted with chloroform three times
13. washthe extract chloroform layer is washed with aqueous sodium bicarbonate solution and water
14. customdried
15. distillationThe chloroform is distilled off under reduced pressure and to the residue
16. customobtained
17. filtrationcollected by suction filtration
18. customrecrystallized from isopropanol/methanol (1/1)